Blood Transfusion Dr Emer Lawlor, IBTS3rd February 2003 : Blood Transfusion Dr Emer Lawlor, IBTS 3rd February 2003


First Blood Transfusions: First Blood Transfusions 1628 1665-’66 1667 Harvey Discovered Circulation of Blood Wilkins & Lower Transfusions from dog to dog Jean-Baptiste Denis Performed first recorded blood transfusions from animals to humans


19th Century Transfusions: 19th Century Transfusions 1818 James Blundell, Obstetrician First transfusion of human to human


Slide4: Early transfusion: Paris, France


Slide5: 20th Century Transfusions 1901 Karl Landsteiner Discovers A, B, O Blood Groups


Slide6: 20th Century Transfusions 1902 1907 AB Group discovered Importance of crossmatching blood between donor & recipient 1914 Sodium Citrate proposed as anticoagulant 1936 1940 First Blood Bank: Barcelona, Spanish Civil War Levine & Landsteiner, Rhesus blood Group System


Bad Blood: France, Switzerland, Italy, Netherlands, Germany, Denmark, Ireland, Australia, New Zealand, Canada, USA Japan Bad Blood


Aims of Transfusion Centre: Aims of Transfusion Centre Provision of Blood of the best possible quality and safety for the patient receiving it To care for the donor - ensure act of donation does not harm donor


Blood Supply Chain: Blood Supply Chain Blood Donor Screening Criteria Donation Process Donation Testing Component preparation Plasma Products


Donor Screening: Donor Screening Self deferral of ‘At Risk’ groups Health Questionnaire Microbiological screening of each donation


Blood Donor Criteria: Blood Donor Criteria Age 17-65 (new donors until 60) Weight > 50kg ( 7st 12Ibs) General health Specific illnesses Contact with infection


Blood Donor Criteria: Blood Donor Criteria HIV,Hepatitis risk Medication CJD Hb > 13 M; >12 F


Haemoglobin Testing : Haemoglobin Testing


Alternatives to Voluntary Donors: Autologous : Alternatives to Voluntary Donors: Autologous 5-10% of patients are fit to predeposit autologous blood Orthopaedic, Plastic Surgery, Gynaecology Up to 5 units can be predeposited/1 week Increased donor reactions Still have risk of : Clerical error, Bacterial Infections


Alternatives to Voluntary Donors: Directed: Alternatives to Voluntary Donors: Directed Relatives or friends Not demonstrably safer Not voluntary Viral marker rates higher as often first time donors TA-GVHD


Blood Donation: Blood Donation 475mls Blood + 63mls anticoagulant Red Cells Plasma Buffy Coat Platelets Red Cells + Optimal Additive Solution Saline Adenine SAGM Glucose Mannitol Expiry date 35 days


Blood Components and Products: Blood Components and Products


Blood Component Production: Blood Component Production


Blood Component Production: Blood Component Production


Leucodepletion: Leucodepletion Universal leucodepletion introduced in 1999 to reduce the risk of vCJD transmission by blood other benefits - less febrile reactions, less alloimmunisation, less GVHD, ? reduce immunosuppresssive effects


Leucodepletion: Leucodepletion


Platelets : Platelets Pools prepared from buffycoats of whole blood donations (4 donations)- Apheresis concentrates from one donor using a cell separator pool/apheresis pack (250mls) = standard adult dose


Blood Donation Testing : Blood Donation Testing Microbiology markers Blood grouping and screening for high titre antibodies Quality monitoring


Slide24: O B A


ABO Groups: ABO Groups


Frequency of ABO & Rh(D) Groups in Ireland: Frequency of ABO & Rh(D) Groups in Ireland Group O 56% Group A 31% Group B 11% Group AB 2.5% Rh (D) positive 85% Rh (D) negative 15%


ABO Grouping : ABO Grouping Test Reagents Patient Red Cells


Slide28: Cells v Serum Serum v Cells


Microbiology testing : Microbiology testing Current anti HIV 1+2 HIV PCR HBsag HBc assay anti HCV HCV PCR anti HTLV1/2 syphilis anti CMV Future Bacterial culture of components Prions


Hospital Blood Transfusion Laboratory : Hospital Blood Transfusion Laboratory Patient/donor testing and product selection and issue


Tests prior to transfusion: Tests prior to transfusion ABO & Rh typing Antibody screen Compatibility Test (x-match) Donor red cells + patients serum Saline and LISS Coombs IBTS Hospital Donor Patient ABO & Rh typing Antibody screen Donor


Slide32: Antigens on Red Cells


Blood Group Antibodies: Blood Group Antibodies 1. Naturally occurring: - ABO - Anti-Hi, P1, E Immune 2. Pregnancy: - Rhesus, Kell, Fya + Others 3. Transfusion: - Rh, Kell, Fy, JKa + Others


Slide34: Weak reactions often difficult to interpret. Can also be downgraded due to shaking the completed test. Conventional Testing.


Principle of Gel Technology: Principle of Gel Technology The sephadex gel matrix acts as a sieve. Large agglutinates remain on or near the top of the gel interface. Smaller agglutinates pass partway through the gel, depending on size. Unagglutinated cells pass to the base of the microtube


Slide37: ABO/Rh Typing Group B RhD positive


Antibody Screening: Antibody Screening Positive antibody screen. Antibody could cause a transfusion reaction or affect an unborn baby.


Purpose of Crossmatch: Purpose of Crossmatch Detect unsuspected ABO incompatibility Donor centre Error in laboratory Detection of unsuspected antibodies in <1% cases


Crossmatching: Crossmatching Donor and patient compatible. Unit safe to transfuse. Patient B Positive Recipient Serum Donor Red Cells ABO Group Crossmatch


Electronic Crossmatch: Electronic Crossmatch Donor units Repeat ABO Rh groups performed on all donor units Automated Grouping Validated computer software to ensure that ABO incompatible units cannot be selected for patient


Blood Component Storage: Blood Component Storage Whole blood/red cells - 2-6C for up to 35 days use within 5 hours of removal from blood fridge Platelets -20-24C on agitator for 5 days SD Fresh frozen plasma ( FFP) for 6 months - use within 4 hrs of thawing Cryoprecipitate -30C use within 4 hours of thawing


Haemovigilance Looping the Loop : Haemovigilance Looping the Loop Safety of the Transfusion Chain from Vein to Vein Right Blood Right Patient Right Time = + + 


Transfusion Chain: Transfusion Chain Supply from Transfusion Centre Patient and sample identification Transport of sample to laboratory Laboratory ordering/testing process Storage Delivery of blood unit to patient Administration Monitoring Adverse Reaction reporting Guidelines, Audit and Review (outside loop)


Slide45: Transfusion Centre Blood Supplied Laboratory Ordering Testing Storage Haemovigilance Adverse Reaction reporting Guidelines, Audit & review Hospital patient & sample Identification Patient Blood Administered Monitored Transfusion Chain


NHO Incidents (category) 1999-2001: NHO Incidents (category) 1999-2001


Transfusion Chain: Transfusion Chain Supply from Transfusion Centre Patient and sample identification Transport of sample to laboratory Laboratory ordering/testing process Storage Delivery of blood unit to patient Administration Monitoring Adverse Reaction reporting Guidelines, Audit and Review


IBCT (n=31) ‘Site of First Error’: IBCT (n=31) ‘Site of First Error’


Wrong Pre-Transfusion Samples: Wrong Pre-Transfusion Samples 2 cases in the first two years of NHO reporting NHO audit 2000: 40% samples not labelled at bedside as per guidelines or prelabelled Untoward incident reports St Elsewhere’s 2000 8 wrong patient samples bled samples out of hours non phlebotomy staff prelabelled tubes musical beds Near Misses only because lab had historic group on patient!


Wrong ABO Group - Case 1: Wrong ABO Group - Case 1 Pre transfusion sample was taken from wrong patient. Patient received an ABO incompatible transfusion. Transfusion reaction investigations led to the identification of multiple errors. NHO Report, 2001


Wrong ABO Group (Cases 5 & 6): Wrong ABO Group (Cases 5 & 6) Two patients in the same ward, one Group O, other Group A, received blood crossmatched for each other Remote checking of units Failure to positively identify the patients Error detected by nursing staff following commencement of the transfusion. Transfusion reaction in O patient who received 100mls A red cells , NHO Report, 2001


Slide52: Immediate Haemolytic Transfusion Reactions IgM Anti A Complement Activated C1-9 Intravascular Haemolysis A antigen


Causes of error in deaths due to haemolytic reactions: Causes of error in deaths due to haemolytic reactions Blood given to wrong person Breach of identification procedures sample taken from wrong person given to person with same surname given to roommate Blood Bank errors Identification errors Wrong blood issued Serological errors 49% 13% 29%


The Final Check  How Good is It ?: The Final Check How Good is It ? 20 of 31 cases (ie.64.5%) the bedside checking procedure failed. May not detect errors of sampling in the transfusion laboratory


Accident waiting to happen?: Accident waiting to happen? Reported incidents 1/600,000 fatalities Near-Miss Events ???????? 1/12,000 incorrect units administered 1/30,000 ABO incompatible transfusions Kaplan & Battles 2001


Estimates of the risk of post-transfusion complications (US Figures): Estimates of the risk of post-transfusion complications (US Figures)


Immediate Hazards of Blood Transfusion : Immediate Hazards of Blood Transfusion Simple Febrile reactions Allergic or anaphylactoid reactions ABO incompatibility leading to acute hemolysis Septic shock due to bacterial contamination Transfusion Associated Circulatory Overload Transfusion Related Acute Lung injury


Slide58: Immediate complications (1-6 h) Immunological Febrile, non-haemolytic Allergic /Anaphylactic Haemolytic transfusion reaction Transfusion Related Acute Lung Injury (TRALI) Non-Immunological Congestive Cardiac Failure Bacterial Contamination Haemolysis-heat damage, freezing, hypotonic fluids Embolism


Febrile Nonhaemolytic Transfusion Reactions (FNHTR): Febrile Nonhaemolytic Transfusion Reactions (FNHTR) Definition: ~1oC rise in temperature and/or chills Incidence 0.5% per unit transfused Alloimmunisation to HLA antigens-pregnancy, previous transfusion Cytokine generation during component storage e.g. platelets Bacterial contamination of blood component Importance: differentiate from ABO, HTR possibility of sepsis from infected unit: platelet 1:7,000 red cells 1:33,000


Urticarial Reactions: Urticarial Reactions 1-3% of transfusions Slow/Stop the transfusion rate Administer iv antibodies e.g chlorpheniramine 10-20 mg If no further progression after 30 mins transfusion may proceed normally Prevention: prophylactic antihistamines


Delayed Hazards: Delayed Hazards Delayed Hemolytic Transfusion Reactions Post Transfusion Purpura Transfusion Associated Graft versus Host Disease Viral infection - parasitic infections ?prions Immunosuppression Iron overload in multi- transfused recipients


Frequency of Transfusion Adverse Events : Frequency of Transfusion Adverse Events Transfusion Associated Circulatory Overload 1:200 TRALI 1:5,000 ABO incompatible transfusion 1;30,000-60,000 Severe Anaphylactoid reaction 1:20,000 GVHD/Post Transfusion Purpura 1:750,000 to 1:1mill Bacterial infection Red Cells Platelets 1:7,000 Viral infection in Ireland - HIV 1:3.3 million - HCV 1:1 million - HBV 1:500,000


Transfusion Associated Circulatory Overload (TACO): Transfusion Associated Circulatory Overload (TACO) 1% of transfusions are complicated by TACO dysnoea, hypertension, crepitations,O2 sats Risk of volume overload/respiratory distress especially in the small and/or elderly patient Largely avoidable by careful attention to fluid balance


Transfusion Related Acute Lung Injury : Transfusion Related Acute Lung Injury 3rd commonest cause of death from transfusion 89% associated with Granulocyte antibodies or HLA antibodies in donor Donor antibodies react with patient white cells Aggregates in lungs Neutrophil priming by lipid ? Older components 2 Hit hypothesis-underlying condition ? haematological malignancy, ?cardiac


Slide65: CXR - 21/11/01


Slide66: CXR - 24/11/01


Graft versus Host Disease: Graft versus Host Disease Rarely reported but virtually always fatal Occurs in immunosuppressed patients In normal patients where donor is HLA homozygous and patient shares a haplotype allowing proliferation and expansion of donor lymphocytes Rare but occurrence commoner where fresh blood, donations from relatives, or where there is a restricted genetic pool i.e. Japan Prevented by irradiation of product


TA-GVHD: TA-GVHD 1-6 weeks post transfusion Fever Rash Liver dysfunction Diarrhoea Pancytopenia Skin/bone marrow biopsy Presence circulating donor lymphocytes


Post-Transfusion Purpura: Post-Transfusion Purpura Thrombocytopenia 5-12 days post transfusion associated with anti HPA antibodies in the patient Shot 11 cases All women previous pregnancies 4 previously transfused Platelet alloantibody: HPA-1a in 8/9 cases Rx IvIg


Bacterial Contamination: Bacterial Contamination Infective shock 1:2 million units transfused 15 cases reported to SHOT since 1996 5 fatalities largest cause of infection related deaths from blood transfusion


Prevention of Transmissible Disease: Prevention of Transmissible Disease Careful selection of Donors Exclude IVDU Homosexuals/bisexuals promiscuity Other exposures e.g. visits to malaria areas Laboratory Screening HIV 1 + 2 & HIV PCR HCV & HCV PCR HBsAg + Core Antibody VDRL HTLV 1+2


Sources of Risk: Sources of Risk Infectious, but seronegative window period Immunosilent infection Variants of known agents Laboratory error New agents for which no test available Unknown agents


‘Window period’: ‘Window period’ HIV 22 days HBV 60 days HCV 80 days


Slide74: HIV Markers During Early Infection


Slide75: HCV Markers During Early Infection


Residual Risk of Transfusion Transmitted Disease: Residual Risk of Transfusion Transmitted Disease HIV 1:3000 000 HCV 1: 500 000 HBV 1: 100 000 JOR after Shreiber et al NEJM 1996


Risk of Dying in any 1 year: Risk of Dying in any 1 year Risk Estimate RTA 1: 8 000 Playing soccer 1: 25 000 Homicide 1: 100 000 Train Accident 1: 100 000-1:16 Lightning 1: 1 000 000


Nucleic Acid Amplification Testing NAT IBTS: Nucleic Acid Amplification Testing NAT IBTS HCV NAT SNBTS Nov 99 HIV NAT Sept 01 467, 694 donations screened No HCV RNA, anti-HCV neg detected No HIV NAT UK 3: 3,500,000 HCV RNA pos


Viral Treatment of Blood Components: Viral Treatment of Blood Components Solvent detergent FFP (pooled-600-1500 donations) from voluntary American donors has replaced single unit FFP Use of psoralen (S59) Rx platelets under investigation


Other Infectious Risks: Other Infectious Risks Viruses Parvo B19, CMV,EBV, HAV West Nile Virus Parasites Malaria. Trypanosomiasis Babesiosis Prions-vCJD


What is a Prion?: What is a Prion? Proteinaceous infectious particle resistant to most procedures that modify nucleic acids in blood


Human CJD: Human CJD Type Cause Sporadic Idiopathic Genetic Inherited, PrP mutation Iatrogenic medical accident Variant BSR via diet


Slide83: Number of Cases of BSE Reported in the United Kingdom


Slide84: vCJD cases in the UK Source: Department of Health (UK) * To 31st August, 2001


What next? Inadvertent Population Exposure: What next? Inadvertent Population Exposure Bovine BSE Human vCJD Human vCJD by iatrogenic spread


Can CJD be transmitted through blood?: Can CJD be transmitted through blood? Epidemiological - case-control studies - lookback - surveillance e.g. haemophiliacs


vCJD and blood transfusion: vCJD and blood transfusion Is there a risk? no documented evidence of transfusion transmission in humans putative infective agent found in lymphoid tissue BSE transmissible by blood from sheep to sheep


CJD Blood Donor Exclusions: CJD Blood Donor Exclusions 5 year Residence in UK 1980-1996 dementia chronic neurological disorder personal or family hx of CJD recipients of human pituitary hormones corneal transplant recipients brain surgery pre 1992


vCJD and Blood Transfusion: vCJD and Blood Transfusion Current Precautions Donor exclusion criteria UK, Irish plasma not used for fractionation 100% leucodepletion of all components


FDA TSEAC 28-29 June, 2001: FDA TSEAC 28-29 June, 2001 Indigenous risk assessment in European countries UK 98% of total risk France 5% of UK risk Rest of Europe 1.5% of UK risk


Protective Measures: Protective Measures Sourcing: country Sourcing: donor Processing Testing Appropriate use of blood/alternatives


West Nile Virus : West Nile Virus Flavivirus natural host birds,mammals spread by mosquito 43 States in US 80% cases asymptomatic 20% mild illness 1% encephalitis 3989 cases -259 deaths 30 related to Transplant /Transfusion


Rh Haemolytic Disease: Rh Haemolytic Disease Father RhD Pos DD, Dd Mother RhD Neg dd Mother produces anti-D antibodies Neonatal jaundice anemia, hydrops intrauterine death Next Rh Pos Babies Baby RBC RhD+ Placenta


Prevention & treatment of Rh Haemolytic Disease: Prevention & treatment of Rh Haemolytic Disease Prevention: Anti-D Immunoglobulin Incidence reduced from 18% to 1% Treatment of Affected Child Exchange Transfusion Monitoring in utero Ultrasound Amniocentesis Cordocentesis Intrauterine Transfusion


Slide95: Haemolytic Disease of the Newborn